• Bulletin of the Korean Chemical Society
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• v.26 no.12
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• pp.1975-1980
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• 2005

A series of substituted rutaecarpines were prepared by employing Fischer indole synthesis as key step and their inhibitory activities on COX-1 and 2 as well as selectivity on COX-2 were evaluated. The compounds with a methanesulfonyl and a bromo group at C10 showed promising inhibitory activity ($IC_{50}$ = 0.27, 0.35 $\mu$M, respectively) with selectivity.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.1
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• pp.254-259
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• 2004

Jeongshin-tang (JST) is a Korean herbal prescription, which has been successfully applied for the various neuronal diseases. However, it's effect remains unknown in experimental models. To investigate the biological effect of JST in Alzheimer's disease (AD) in vitro model, we analized the production of interleukin (IL)-6 and IL-8, and expression of cyclooxygenase (COX)-2 in IL-1β plus β-amyloid [25-35] fragment (A)-stimulated human astrocytoma cell line U373MG. JST alone had no effect on the cell viability. The production of IL-6 and IL-8 was significantly inhibited by pretreatment with JST (1mg/㎖) on IL-1β plus A-stimulated U373MG cells. Maximal inhibition rate of IL-6 and IL-8 production by JST was about 41.22% (P<0.01) and 34.45% (P<0.05), respectively. The expression level of COX-2 protein was up-regulated by IL-1β plus A but the increased level of COX-2 was inhibited by pretreatment with JST (1 mg/㎖). These data indicate that JST has a regulatory effect on cytokine production and COX-2 expression, which might explain it's beneficial effect in the treatment of AD.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2000.04a
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• pp.10-14
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• 2000

The cycloooxygenase enzymes catalyze the oxidative conversion of arachidonic acid into prostag1andin H$_2$Which mediates both benificial and pathological effects. The COX-1 is constitutively expressed in most tissues and in blood platelets wherease the expression of COX-2 isoform is induced in response to inflmmatory stimuli such as cyctokynes. Thus the identification of a novel COX-2 selective inhibitor should offer excellent antiinflammatory activity with minimal side effects such as gastrointestinal toxicity. Recently, a group of structurally unique and biologically active pimarane diterpenoids has been isolated from indigenous Korean medicinal plants. These new diterpenoids turned out to be potential analgesic and antiinflammatory agent due to their potent inhibitory activities of prostaglandin synthesis. We have also found that the inhibition of PGE$_2$synthesis is attributed to the potent COX inhibition by pimarane diterpenoid in arachidonic acid cascade. In conjunction with development of new analgesic and nonsteroidal antiinflammatory agent, a series of works on these diterpenoids have been extensively carried out in our laboratories. These efforts involve the structure-activity relationship of pimaradienoic acid, molecular modelings and COX inibitory activities as well as actiinflammatory effects of its structural analogues. In addition, the total syntheses of the new natural pimarane diterpenoids, their stereoisomers and other structural variants were intensively investigated.

• Preventive Nutrition and Food Science
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• v.11 no.1
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• pp.1-5
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• 2006

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of linoleic acid that have been used to reduce the incidence, growth and metastasis of breast, colon, prostate and gastric cancer in animals. CLA could reduce tumor growth by altering angiogenesis; a process requiring associated angiogenic factors such as vascular endothelial growth factor (VEGF). In this study, we determined whether CLA could modulate the expression of VEGF in murine mammary tumor cells and adipocytes. The c9, t11-CLA isomer reduced VEGF transcripts and protein when mammary tumor cells were stimulated with PMA. That isomer also reduced VEGF expression in un stimulated mouse 3T3-L1 adipocytes. Since VEGF can be regulated by cyclooxygenase-2 (COX-2), we determined whether CLA could alter COX-2 enzyme expression and $PGE_2$ production. The c9, t11-CLA isomer reduced not only COX-2 enzyme expression but also $PGE_2$ production. Thus, c9, t11-CLA could modulate neovascularization by alteration of VEGF expression from mammary tumor cells and adipocytes by reducing COX-2 metabolites.

• The Journal of Korean Medicine
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• v.26 no.3 s.63
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• pp.215-227
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• 2005

Objectives : This study was carried out to investigate the effects of Pyungjintang on indomethacin-induced gastric mucosal lesions of mire. Methods : Experimental mice were classified into not-treated group (NOR group), gastro-inflammation elicitated group (CON group), misoprostol-administered group after gastro-inflammation elicitation (MA group), and Pyungjintang-administered group after gastro-inflammation elicitation (PA group). This study examined the morphological change, distribution of mast cells, mucus surface cells, neutral mucus secreting cells, acid mucus secreting cells, PNA reaction, angiogenesis (MIP-2), COX-1, Hsp70, NF-kB p50, COX-2IL-12B, ICAM-1, BrdU and apoptotic cells of gastric mucosa. Results : 1. The scars of diapedesis, dilatation of right gastric artery and the hemorrhagic erosions of gastric mucosa were reduced in the MA and PA groups. 2. Gastric perforation was observed in the gastro-inflammation elicitated group, but not in the MA and PA groups. 3. The COX-1 positive cellsl, cell proliferation of gastric mucosa, neutral mucus secreting ce31s, acid mucus secreting cells and PNA positive reaction of surface mucus cells were increased in the MA and PA groups. 4. The distribution of apoptotic cells, mast cells, MIP-2, Hsp70, NF-kB p50, COX-2, IL-l2B and ICAM-1 were decreased in the MA and PA groups. Conclusions : Pyungjintang had excellent effects on indomethacin-induced gastric mucosal lesions in mice.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.15 no.1
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• pp.91-100
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• 2004

Objectives：The effects of repeated maternal separation on the expression of glucocorticoid receptor (GR) and cyclooxygenase-2(COX-2) in the hippocampus of rat pups at preweanling stage were evaluated. Methods：The experimental, Repeated Maternal Separation group(N=4) was separated from the mother for four hours a day over a period of ten days beginning with postnatal day 4. The Control group(N=4), on the other hand, did not separated from the mother at all. GR and COX-2 expression in the hippocampus was examined by immunohistochemistry on postnatal day 14. Results：It was determined that the number of GR-immunopositive cells in the dentate gyrus of the hippocampus was significantly increased in the Repeated Maternal Separation group. The numbers of COX-2-immunopositive cells in the CA1 and CA3 were also significantly higher in the Repeated Maternal Separation group. Conclusion：These results suggest that maternal separation may be a significant developmental stress that induces GR and COX-2 expression in the hippocampus of developing pups.

• The Korea Journal of Herbology
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• v.28 no.2
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• pp.93-101
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• 2013

Objects : Baicalein is a major bioactive flavonoid component of Scutellaria baicalensis Georgi that shows a wide range of biological activities, including neuroprotections and anti-inflammatory actions. Hence it is a potential therapeutic material for the treatment of neuroinflammation. In this study, we investigated the modulatory effect of baicalein on neuroinflammation. Method : Pro-inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 mRNA), COX-2 mRNA expression and microglial activation in the brain tissue is induced by systemic lipopolysaccharide (LPS) treatment in C57BL/6 mice. Baicalein was treated orally with 10, 20, and 30 mg/kg 1 hour prior to the LPS (3 mg/kg, i.p.) injection. TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and COX-2 mRNA expression in the brain tissue was measured by the quantitative real-time polymerase chain reaction(PCR) method. Iba1 expression in the brain was measured by western blotting method. Microglia was observed with immunohistochemistry. Results : Baicalein 30 mg/kg significantly attenuated the expression of TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and COX-2 mRNA in the brain tissue. Baicalein 20 mg/kg significantly attenuated the expression of IL-6 mRNA in the brain tissue. Baicalein 30 mg/kg significantly attenuated the expression of Iba1 protein expression in the brain tissue. Baicalein 30 mg/kg significantly decreased the number and cell size of microglia in the cerebral cortex and hypothalamic region and the area percentage of Iba1-expressed microglia in the hippocampus. Conclusion : These results demonstrated that baicalein attenuates LPS induced neuroinflammation in the mice via reduction of pro-inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$, IL-6), COX-2 mRNA expression and microglial activation.

• Biomedical Science Letters
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• v.21 no.4
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• pp.188-197
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• 2015

In this study, we investigated the effect of rice bran water extract fermented with Lactobacillus plantarum Hong (RBLw), on activities of cyclooxygenase-1 (COX-1) and thromboxane $A_2$ synthase (TXAS), thromboxane $A_2$ ($TXA_2$) production associated microsomal enzymes and evaluated its the antiplatelet effect. RBLw, containing 13.5 mg of ferulic acid, dose-dependently inhibited ADP-induced platelet aggregation, and inhibited the production of $TXA_2$, an aggregation molecule. In addition, RBLw directly inhibited COX-1 activity in a dose-dependent manner, but not TXAS activity in platelet microsomal fraction having cytochrome c reductase (an endoplasmic reticulum marker enzyme) activity and expressing COX-1 (72 kDa) and TXAS (60.5 kDa) proteins. These results suggest that RBLw selectively inhibited the activity of COX-1 rather than TXAS to attenuate $TXA_2$ production in ADP-activated platelets. Thus, we demonstrate that RBLw might have direct COX-1 antagonistic function for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.11a
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• pp.154-154
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• 2004

• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.27-32
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• 2011

The activation of microglia induces the overproduction of inflammatory mediators that are responsible for the neurodegenerative disorders including Alzheimer's disease and Parkinson's disease. The large amounts of prostaglandin $E_2$ ($PGE_2$) produced by inducible cyclooxygenase (COX-2) is one of the main inflammatory mediators that can contribute to neurodegeneration. The inhibition of COX-2 thus may provide therapeutic strategy for the treatment of neurodegenerative diseases. From the activity-guided purification of EtOAc soluble fraction of Siegesbeckia glabrescens, four compounds were isolated as inhibitors of $PGE_2$ production in LPS-activated microglia. Their structures were determined as 3, 4'-dimethylquercetin (1), 3, 7-dimethylquercetin (2), 3-methylquercetin (3) and 3, 7, 4'-trimethylquercetin (4) by the mass and NMR spectral data analysis. The compounds 1-4 showed dose-dependent inhibition of $PGE_2$ production in LPS-activated microglia with their $IC_{50}$ values of 7.1, 4.9, 4.4, $12.4\;{\mu}M$ respectively. They reduced the expression of protein and mRNA of COX-2 through the inhibition of I-${\kappa}B{\alpha}$ degradation and NF-$\kappa}B$ activity that were correlated with the inactivation of p38 and ERK. Therefore the active compounds from Siegesbeckia glabrescens may have therapeutic effects on neuro-inflammatory diseases through the inhibition of overproduction of $PGE_2$ and suppression of COX-2 overexpression.